Chronic Graft Versus Host Disease in Skin

Chronic graft versus host disease affecting the skin is a serious complication that can occur after a stem cell or bone marrow transplant, when the donated cells attack the recipient’s body. The skin is the most commonly affected organ, with symptoms appearing in approximately 70 percent of patients who develop this condition.

Table of contents

• What is Chronic Graft Versus Host Disease in Skin
• What Causes This Condition
• Who Gets Chronic GVHD in Skin
• Symptoms and Clinical Features
• How It Is Diagnosed
• Treatment Options
• Living with the Condition
• Complications and Long-term Effects

What is Chronic Graft Versus Host Disease in Skin

Chronic graft versus host disease, or chronic GVHD, is a condition that can occur after a stem cell transplant or bone marrow transplant from another person (called an allogeneic transplant). In this condition, the donor’s immune cells view the recipient’s body as foreign and attack the recipient’s tissues and organs^[1].

The skin is not just the most common but usually the first organ to show signs of chronic GVHD. Approximately 70 percent of patients who develop chronic GVHD will experience skin involvement^[3]. This makes the role of recognizing skin changes particularly important for early diagnosis and treatment.

Chronic GVHD is different from acute GVHD. While acute GVHD typically occurs within the first 100 days after transplant, chronic GVHD can appear any time after transplant, though most cases start within the first two years^[4]. The two conditions are now classified more by their symptoms and clinical signs rather than just timing of onset^[2].

D89.81; D89.810; D89.811; T86.09

GVHD, chronic graft-versus-host disease, graft versus host disease chronic, gvhd chronic

• Skin
• Hair follicles
• Nails
• Connective tissue

What Causes This Condition

Chronic GVHD occurs when T lymphocytes (a type of white blood cell) in the donated tissue recognize the recipient’s body as foreign and attack it^[2]. The exact cause of chronic GVHD is not fully understood, but it likely results from a complex interaction between the donor and recipient cells^[5].

In people with chronic GVHD, the immune system becomes unbalanced. It overreacts, creating too many of some cells and molecules while not producing enough of others. This leads to two main problems: inflammation (swelling that occurs as the body tries to protect itself) and fibrosis (the growth of scar tissue that hardens and prevents organs from working properly)^[6].

Chronic GVHD is largely an inflammatory and fibrotic process, which is different from acute GVHD that more commonly reflects cell death and tissue damage^[1]. In the skin specifically, chronic GVHD affects different layers of the skin as well as the connective tissue beneath it^[3].

Who Gets Chronic GVHD in Skin

Chronic GVHD can affect between 40 and 60 percent of patients who receive an allogeneic stem cell transplant, depending on various factors related to both the donor and the recipient^[1].

Several factors increase the risk of developing chronic GVHD after a transplant^[2]:

• Immune mismatch between donor and recipient (particularly human leucocyte antigen or HLA mismatch)
• Older age of either the donor or recipient
• Gender differences between donor and recipient
• History of pregnancy or blood transfusions in the donor
• Use of peripheral blood stem cells rather than bone marrow
• Previous acute GVHD in the recipient
• Splenectomy (removal of the spleen) in the recipient

Although extremely rare, chronic GVHD may also occur after transfusion of non-irradiated blood products or after solid organ transplantation^[2].

Symptoms and Clinical Features

Chronic GVHD affecting the skin can cause a wide range of symptoms. The condition may look similar to well-known inflammatory and autoimmune disorders, which can sometimes make diagnosis challenging^[1].

Skin Changes

The skin changes in chronic GVHD can include^[2][3]:

• Poikiloderma: a condition causing skin thinning and changes in skin color
• Features similar to lichen planus: raised patches or bumps on the skin
• Sclerotic features: thick and tight skin that feels hard to the touch
• Features similar to morphoea or lichen sclerosus: areas of hardened, thickened skin
• Loss of skin color (hypopigmentation)
• Spots on the skin
• Intense itching
• Dry, cracking skin

Hair and Nail Changes

Chronic GVHD can also affect hair and nails^[2][3]:

• Hair loss on the scalp (scarring or non-scarring alopecia)
• Loss of body hair
• Scaling of the scalp
• Nails with lengthwise ridges or splitting
• Onycholysis (nail separating from the nail bed)
• Pterygium (skin growing over the nail)
• Complete nail loss
• Brittle, cracked, or chipped nails

Other Skin-Related Symptoms

Additional symptoms that patients commonly report include decreased range of motion in joints due to skin tightening, muscle cramps, and overall fatigue^[3]. The physical tightening of skin can lead to contractures (permanent tightening of muscles and tendons) and joint stiffness^[2].

Itchy skin is one of the first symptoms, often appearing even before visible skin changes occur^[7]. This itching, along with dry mouth, reduced energy, and emotional stress, are among the most commonly reported symptoms affecting quality of life^[2].

How It Is Diagnosed

Diagnosing chronic GVHD in the skin can be challenging because symptoms may resemble other skin conditions. The overlapping of clinical and microscopic findings with other diseases can make it difficult to establish a definite diagnosis^[1].

Doctors diagnose chronic GVHD based on several factors^[6]:

• A thorough physical examination
• Review of symptoms and their timing
• Various tests to rule out other conditions
• In some cases, a skin biopsy (taking a small sample of skin tissue for examination under a microscope)

Doctors grade chronic GVHD by looking at the number of organs involved and how severe the condition is. Based on this information, they assign a grade: mild, moderate, or severe^[8]. This grading helps doctors plan the most appropriate treatment.

It is important to report any changes in your skin, range of motion, nails, or hair to your transplant doctor promptly so that treatment can be started early^[3].

Treatment Options

The goals of treatment for chronic GVHD in the skin are to control symptoms, prevent organ damage, improve physical function, and improve quality of life^[3]. Treatment typically involves continuing the original immunosuppressive medications and may require long-term therapy^[8].

First-Line Treatment

Corticosteroids, particularly prednisone, are the primary treatment for chronic GVHD. About two-thirds of people will see improvement after six months of treatment^[3]. Steroids work by dampening down the immune system so it doesn’t attack the body’s tissues^[8].

Steroids may be used alone or in combination with another medicine called ciclosporin (also spelled cyclosporine). These medicines can be taken by mouth or, in some cases, given directly into a vein^[8].

Second-Line Treatments

If prednisone fails to control the condition, there are more than 20 second-line treatments that doctors can try^[3]. These include^[8][10]:

• Targeted cancer drugs such as sirolimus, imatinib, or ruxolitinib
• Monoclonal antibodies such as rituximab
• Medicines that suppress the immune system such as mycophenolate mofetil (MMF) or tacrolimus
• Chemotherapy drugs such as methotrexate
• Light treatments such as extracorporeal photopheresis (ECP) or PUVA (Psoralen ultraviolet light A)

Treatment of patients who don’t respond to steroids remains a challenge, and no single agent has been agreed upon as the best second-line therapy^[1].

Skin-Specific Treatments

Several treatments target the skin directly and may be used alone or as additional therapy to help reduce the need for systemic immunosuppression^[1]. For skin chronic GVHD specifically, treatment includes^[8]:

• Keeping skin clean with unperfumed soaps
• Regular moisturizing
• Steroid creams applied to affected areas
• Rarely, a cream called tacrolimus for small affected areas
• Antihistamine medicines to help with itching
• Light therapy treatments for severe cases

Your doctor may refer you to a skin specialist called a dermatologist for additional care^[8].

Living with the Condition

Chronic GVHD affecting the skin can last for many months or even years, which means treatment needs to continue long-term^[8]. The average length of time people have chronic GVHD is between one and three years, though some people may have it longer^[12].

Self-Care Measures

There are several things you can do to help keep your skin more comfortable^[8][11]:

• Use lots of moisturizing creams to relieve itchy or dry skin
• Apply cream generously at night and wear old nightclothes and socks
• Wear cotton clothes
• Avoid getting too hot or too cold
• Use lukewarm (not hot) water when washing
• Let your skin dry in the air or gently pat it dry instead of rubbing
• Protect your skin from the sun by covering up, staying in the shade, and using sunscreen
• Drink plenty of water

Emotional and Practical Challenges

Chronic GVHD can be very difficult to cope with, especially after going through intensive transplant treatment. Dealing with long-term, uncomfortable symptoms can be hard to accept, and you may feel very low or anxious^[12].

The physical changes from chronic skin GVHD and steroid treatment can affect how you look, which might affect your self-esteem and how you think others see you. GVHD affecting muscles and joints can be painful and affect your ability to move around. You might also feel very tired^[12].

Managing chronic skin GVHD takes up a lot of time, and you might need help from family members or others you live with^[8]. The physical and emotional changes you experience might affect your relationships^[12].

Getting Support

Support during this time is important. Counseling can help some people, or you may prefer to talk to friends, family, or other people who have similar problems^[12]. Your doctor and specialist nurse can provide advice and information about GVHD and what to expect.

Organizations such as Blood Cancer UK provide information booklets and opportunities to connect with others dealing with blood cancer and transplant-related complications^[12].

Complications and Long-term Effects

Chronic GVHD is associated with high death rates and can have a significant negative impact on quality of life^[1]. It remains a major cause of late death after transplant and is a major factor affecting the health and quality of life of survivors^[13].

Specific complications of chronic skin GVHD include^[2]:

• Difficulty sleeping due to itchy skin
• Increased risk of infection due to immunosuppressive treatment
• Development of fasciitis (inflammation of connective tissue)
• Joint stiffness or contractures due to sclerosis
• Myositis or polymyositis (muscle inflammation)

Patients with chronic skin GVHD have an increased risk of developing skin cancer^[3]. Secondary cancers are more common in people with chronic GVHD, particularly in commonly involved tissues such as mouth and skin, suggesting that chronic inflammation, prolonged exposure to immunosuppressive medications, or immune imbalance may facilitate the development of new cancers^[13].

Let your healthcare team know if you notice any skin changes that aren’t normal for you^[8]. Early detection and treatment are important for managing complications and improving outcomes.